Imagine a technology able to noninvasively identify individual cones in the living human retina and selectively stimulate them to study their contribution to visual perception. This technology could also track retinal functional organization at the border of a visual scotoma to study mechanisms disease and outcomes of treatment regimes. The technology does not yet exist but the current generation of the adaptive optics scanning laser ophthalmoscope (AOSLO), with its unique ability to compensate for retinal motion and image the cone mosaic, comes very close. The remaining obstacle is real time correction of transverse chromatic aberration (TCA) between the infrared beam and a visible light laser beam so that we can repeatedly, continuously and reliably image and stimulate the individual identified cones from day to day. Achieving and validating this capability is the principal goal (Aim 1) of this proposal. The validation of TCA error correction includes both physical (image processing) and innovative perceptual (chromatic shifts) techniques of characterizing the accuracy and reliability of stimulating the center of single cones. The method includes rapid identification of L &M cone classes which is itself a significant advance. In Aim 2, after we map out an array of cones identified by class near the fovea, we will stimulate different single L and M cones within the array while observers judge the intensity, hue and saturation of the flash. This single cone stimulation aim focuses on characterizing the stability of percepts within a cone and consistency across cones of the same class. This step will establish the parameters of cone activation and resultant percepts and clarify any constraints it might impose on future research. Along the way we expect to confirm or discredit hypotheses on the consequences of different cone class neighborhoods around the single probed cone. In Aim 3 we examine mechanisms of light adaptation;does it occur within a single cone? With our superior image stabilization, small steady, intense pedestals delivered to the center of a cone are expected to result in rapid Troxler fading. Once faded, the pedestal may not saturate the incremental test response (as in the Westheimer effect) but instead act largely like a uniform field with a constant cone-selective Weber law behavior. What appeared to be cone saturation may result from eye tremor. The proposed single cone studies will demonstrate the capabilities of the AOSLO. Future studies involving simultaneous and independent stimulation of multiple identified cones will be just as easy to perform and be able to address research questions extending from color to spatial vision in general. PUBLIC HEALTH RELEVANCE: Retinal degeneration includes a diverse class of diseases (e.g., ciliopathies, achromatopsia, and retinal dystrophy) that impact about 1 in 3000 persons, and most cases involve a progressive loss of photoreceptors and concomitant visual impairments. The proposed research will enable a deeper understanding of retinal organization and provide us with the ability to track disease progression at the critical locations and treatment outcomes, which can be important for both fundamental research and clinical patient care.